Faculty Bibliography

Many lines of evidence implicate mitochondria in phenotypic variation: (a) rare mutations in mitochondrial proteins cause metabolic, neurological, and muscular disorders; (b) alterations in oxidative phosphorylation are characteristic of type 2 diabetes, Parkinson disease, Huntington disease, and other diseases; and (c) common missense variants in the mitochondrial genome (mtDNA) have been implicated as having been subject to natural selection for adaptation to cold climates and contributing to "energy deficiency" diseases today. To test the hypothesis that common mtDNA variation influences human physiology and disease, we identified all 144 variants with frequency >1% in Europeans from >900 publicly available European mtDNA sequences and selected 64 tagging single-nucleotide polymorphisms that efficiently capture all common variation (except the hypervariable D-loop). Next, we evaluated the complete set of common mtDNA variants for association with type 2 diabetes in a sample of 3,304 diabetics and 3,304 matched nondiabetic individuals. Association of mtDNA variants with other metabolic traits (body mass index, measures of insulin secretion and action, blood pressure, and cholesterol) was also tested in subsets of this sample. We did not find a significant association of common mtDNA variants with these metabolic phenotypes. Moreover, we failed to identify any physiological effect of alleles that were previously proposed to have been adaptive for energy metabolism in human evolution. More generally, this comprehensive association-testing framework can readily be applied to other diseases for which mitochondrial dysfunction has been implicated.

In the study, which independent experts said was the most conclusive to examine the role of condoms in preventing infection with the virus, women whose male partners used condoms every time they had sexual intercourse had less than half the rate of infection than women whose partners used condoms less than 5 percent of the time. The study was conducted among students at the University of Washington in Seattle. In 2000, four government agencies convened a panel of condom experts to determine the medical accuracy of condom labels. The panel concluded that there was inadequate information about condom use in reducing the risk of all sexually transmitted infections except for the AIDS virus and, among men, gonorrhea, an editorial accompanying the journal article said

In the study, which independent experts said was the most conclusive to examine the role of condoms in preventing infection with the virus, women whose male partners used condoms every time they had sexual intercourse had less than half the rate of infection as did women whose partners used condoms less than 5 percent of the time. The study 'provided a very clear answer' to the question of the protective benefits of condoms and papillomavirus infection, said Dr. James R. Allen, president of the American Social Health Association, an organization in Research Triangle Park, N.C., dedicated to the prevention of sexually transmitted infections. Allen said he was not involved in the study

In the study, which independent experts said was the most conclusive to examine the role of condoms in preventing infection with the virus, women whose male partners used condoms every time they had sexual intercourse had less than half the rate of infection as did women whose partners used condoms less than 5 percent of the time. In 2000, four government agencies convened a panel of condom experts to determine the medical accuracy of condom labels in describing their effectiveness in preventing papillomavirus and other sexually transmitted diseases. The researchers used certain statistical measures to determine the findings in the study. For example, no malignant or precancerous cervical lesions were detected in 32 patient years at risk among women reporting 100 percent condom use by their partners. That compared with 14 such lesions in 97 patient years at risk among women whose partners did not use condoms or who used them less consistently

Reporting in The New England Journal of Medicine, the study's authors said they had recruited 158 scleroderma patients who had early signs of lung damage. The patients, drawn from 13 hospitals in this country, agreed to be assigned randomly to one of two groups, without knowing which one. One group of 79 was to take Cytoxan pills daily for a year. An equal number were to take a placebo, or dummy pill, also for a year. Both groups were monitored for a second year. Many doctors already prescribe Cytoxan for scleroderma patients, in part because earlier, less scientifically rigorous studies hinted at its benefit. But until now no drug for scleroderma patients with lung damage has proved effective in a scientifically controlled study, the type of research that scientists consider the gold standard for assessing benefits and safety of therapies, Dr. [Philip J. Clements] said in an interview

Commander in Chief [Television Program] -- PRESIDENT Mackenzie Allen (Geena Davis) wakes up feeling feverish. She vomits, but still manages to summon the energy to board Air Force One. When she develops abdominal pain, the White House internist diagnoses acute appendicitis and possible rupture -- after simply eliciting severe right lower quadrant abdominal tenderness by palpating her flank. He states she has sepsis (a life- threatening systemic infection) and insists the plane be landed immediately for emergency surgery. At the hospital, the top general surgeon attempts to remove the appendix laparoscopically. But finding a perforated appendix, and with her blood pressure dropping, he switches to an open procedure. The president survives and a day later resumes her duties -- without a full course of intravenous antibiotics or bowel rest

Cardiovascular disease (CVD) is the leading cause of mortality and a major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD deaths. Currently estimation of risk in primary prevention is based on the Framingham risk equations, which inputs traditional risk factors and is helpful in predicting the development of CHD in asymptomatic individuals. However many individuals suffer events in the absence of established risk factors for atherosclerosis and broad based population risk estimations may have little precision when applied to a given individual. To meet the challenge of CHD risk assessment, several tools have been developed to identify atherosclerotic disease in its preclinical stages. This paper aims to incorporate information from coronary artery calcification (CAC) scoring from a computed tomographic "heartscan" (using Electron Beam Tomography (EBT) as the validated prototype) along with current Framingham risk profiling in order to refine risk on an absolute scale by combining imaging and clinical data to affect a more comprehensive calculation of absolute risk in a given individual. For CAC scores above the 75th percentile but <90th percentile, 10 years is added to chronological age, and for CAC scores above the 90th percentile, 20 years is added to current chronological age. Among those in whom a positive CAC score is the norm such as older individuals (men> or =55 years, women> or =65 years) a CAC = 0 will result in an age point score corresponding to the age-group whose median CAC score is zero i.e., 40-44 years for men and 55-59 years for women. The utilization of CAC scores allows the inclusion of sub-clinical disease definition into the context of modifiable risk factors as well as identifies high-risk individuals requiring aggressive treatment.